Phosphorus retention capacity in red ferralitic soil.

In this study the main physical-chemical characteristics of red ferralitic soil to use as substrate in subsurface wetlands was determined. The P-removal was evaluated in a short-term isotherm batch experiment and in a column percolation experiment. The acid characteristic and high content of iron minerals in the red ferralitic soil facilitated the phosphorus removal.

Vertical flow constructed wetlands: kinetics of nutrient and organic matter removal.

The kinetics of organic matter and nutrient removal in a pilot vertical subsurface wetland with red ferralitic soil as substrate were evaluated. The wetland (20 m(2)) was planted with Cyperus alternifolius. The domestic wastewater that was treated in the wetland had undergone a primary treatment consisting of a septic moat and a buffer tank.

Activity cliffs in drug discovery: Dr Jekyll or Mr Hyde?

The impact activity cliffs have on drug discovery is double-edged. For instance, whereas medicinal chemists can take advantage of regions in chemical space rich in activity cliffs, QSAR practitioners need to escape from such regions. The influence of activity cliffs in medicinal chemistry applications is extensively documented.

Model for high-throughput screening of drug immunotoxicity--study of the anti-microbial G1 over peritoneal macrophages using flow cytometry.

Quantitative Structure-Activity (mt-QSAR) techniques may become an important tool for prediction of cytotoxicity and High-throughput Screening (HTS) of drugs to rationalize drug discovery process. In this work, we train and validate by the first time mt-QSAR model using TOPS-MODE approach to calculate drug molecular descriptors and Linear Discriminant Analysis (LDA) function. This model correctly classifies 8258 out of 9000 (Accuracy = 91.

Shannon's, mutual, conditional and joint entropy information indices: generalization of global indices defined from local vertex invariants.

A new mathematical approach is proposed in the definition of molecular descriptors (MDs) based on the application of information theory concepts. This approach stems from a new matrix representation of a molecular graph (G) which is derived from the generalization of an incidence matrix whose row entries correspond to connected subgraphs of a given G, and the calculation of the Shannon's entropy, the negentropy and the standardized information content, plus for the first time, the mutual, conditional and joint entropy-based MDs associated with G. We also define strategies that generalize the definition of global or local invariants from atomic contributions (local vertex invariants, LOVIs), introducing related metrics (norms), means and statistical invariants.

Provisional classification and in silico study of biopharmaceutical system based on caco-2 cell permeability and dose number.

Today, early characterization of drug properties by the Biopharmaceutics Classification System (BCS) has attracted significant attention in pharmaceutical discovery and development. In this direction, the present report provides a systematic study of the development of a BCS-based provisional classification (PBC) for a set of 322 oral drugs. This classification, based on the revised aqueous solubility and the apparent permeability across Caco-2 cell monolayers, displays a high correlation (overall 76%) with the provisional BCS classification published by World Health Organization (WHO).

Computational tools in the discovery of new G-quadruplex ligands with potential anticancer activity.

Guanine-rich sequences found at telomeres and oncogenes have the capacity to form G-quadruplex (G4) structures. It has been found a relationship between the ability to stabilizing G4 structures and anticancer activity. Guanine quadruplexes stabilization and its implication in cancer phenomena is a therapeutic target relatively recent.

Plants genetic manipulation: an approach from intellectual property.

From the end of the 20th century the Biotechnology has experimented a vertiginous advance so far, putting on approval concepts like bio-security and bioethics; becoming this way, the work with the genome of the plants, in a matter is worthy to be reconsidered by the juridical mark that regulates it, in order to moderate the norm to the new scientific context. The Intellectual Property, when recognizing patent rights on products that have incorporate biological material, as well as to the obtainer about the new vegetable varieties obtained, could mean an obstacle that impedes or hinder the access from the society to that product or that variety. In the same way is worthy of consideration, the fact that such products or varieties can be a risk for the human health or the Environment, and a monopoly of commercial exploitation for the holder of the patent or of the obtainer certificate.

Derivatives in discrete mathematics: a novel graph-theoretical invariant for generating new 2/3D molecular descriptors. I. Theory and QSPR application.

In this report, we present a new mathematical approach for describing chemical structures of organic molecules at atomic-molecular level, proposing for the first time the use of the concept of the derivative ([Formula: see text]) of a molecular graph (MG) with respect to a given event (E), to obtain a new family of molecular descriptors (MDs). With this purpose, a new matrix representation of the MG, which generalizes graph's theory's traditional incidence matrix, is introduced. This matrix, denominated the generalized incidence matrix, Q, arises from the Boolean representation of molecular sub-graphs that participate in the formation of the graph molecular skeleton MG and could be complete (representing all possible connected sub-graphs) or constitute sub-graphs of determined orders or types as well as a combination of these.

FDA-approved drugs selected using virtual screening bind specifically to G-quadruplex DNA.

Guanine-rich sequences found in telomeres and oncogene promoters have the ability to form G-quadruplex structures. In this paper we describe the use of a virtual screening assay to search a database of FDA-approved compounds for compounds with the potential to bind G-quadruplex DNA. More than 750 telomerase inhibitors were identified in a literature search as acting through G-quadruplex stabilization, and from evaluation of these compounds, theoretical models capable of discriminating new compounds that bind G-quadruplex DNA were developed.

Characterization and molecular modeling of the inclusion complexes of 2-(2-nitrovinyl) furan (G-0) with cyclodextrines.

The objective of this study was to prepare and characterize complexes of 2-(2-nitrovinyl) furan (G-0) with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) and sulfobutyl ether-β-cyclodextrin (SBE-β-CD). The solid inclusion complexes were prepared using kneading and freeze-drying methods. Phase solubility profiles were used to obtain the apparent stability constants and the complexation efficiency.

Effectiveness of association splitting in reducing unwanted intrusive thoughts in a nonclinical sample.

Background: Association Splitting (AS) is a novel cognitive technique, which has shown some promise for the reduction of obsessive thoughts in patients with obsessive-compulsive disorder (OCD). Its effect on unwanted intrusive thoughts (UITs) in the general population is yet unknown.

Method: Our experimental study tested the effect of AS in 49 participants who reported UITs as a regular problem.

QSPR in oral bioavailability: specificity or integrality?

During the last decade the technological advances in drug discovery changed the absorption, distribution, metabolism, excretion and toxicity (ADMET) profiles of New Chemical Entities (NCEs). Among ADMET processes, absorption plays an important role in the research and development of more effective orally administered drugs. Although significant progress has been made in in vitro, in situ and in vivo experimental determinations of absorption, the development of in silico methodologies has emerged as a cheaper and fast alternative to predict them.

Strategies for pH control in a biofilter packed with sugarcane bagasse for hydrogen sulfide removal.

The biological removal of hydrogen sulfide at low concentration (<120 ppmv) was studied in a laboratory-scale biofilter packed with sugarcane bagasse and inoculated with a sulfur-oxidizing bacterial consortium isolated from activated sludge from a wastewater treatment plant (WWTP). Inlet loads from 1.31 to 20.

A review of QSAR studies to discover new drug-like compounds actives against leishmaniasis and trypanosomiasis.

The neglected tropical diseases (NTDs) affect more than one billion people (one-sixth of the world's population) and occur primarily in undeveloped countries in sub-Saharan Africa, Asia, and Latin America. Available drugs for these diseases are decades old and present an important number of limitations, especially high toxicity and, more recently, the emergence of drug resistance. In the last decade several Quantitative Structure-Activity Relationship (QSAR) studies have been developed in order to identify new organic compounds with activity against the parasites responsible for these diseases, which are reviewed in this paper.

Ligand-based discovery of novel trypanosomicidal drug-like compounds: in silico identification and experimental support.

Two-dimensional bond-based linear indices and linear discriminant analysis are used in this report to perform a quantitative structure-activity relationship study to identify new trypanosomicidal compounds. A database with 143 anti-trypanosomal and 297 compounds having other clinical uses, are utilized to develop the theoretical models. The best discriminant models computed using bond-based linear indices provides accuracies greater than 90 for both training and test sets.

In Silico Prediction of Caco-2 Cell Permeability by a Classification QSAR Approach.

In the present study, 21 validated QSAR models that discriminate compounds with high Caco-2 permeability (Papp ≥8×10(-6)  cm/s) from those with moderate-poor permeability (Papp <8×10(-6)  cm/s) were developed on a novel large dataset of 674 compounds. 20 DRAGON descriptor families were used. The global accuracies of obtained models were ranking between 78-82 %.

Exploring the conformational changes of the ATP binding site of gyrase B from Escherichia coli complexed with different established inhibitors by using molecular dynamics simulation: protein-ligand interactions in the light of the alanine scanning and free energy decomposition methods.

Currently, bacterial diseases cause a death toll around 2 million people a year encouraging the search for new antimicrobial agents. DNA gyrase is a well-established antibacterial target consisting of two subunits, GyrA and GyrB, in a heterodimer A(2)B(2). GyrA is involved in DNA breakage and reunion and GyrB catalyzes the hydrolysis of ATP.

Novel coumarin-based tyrosinase inhibitors discovered by OECD principles-validated QSAR approach from an enlarged, balanced database.

The present work is devoted to the development and application of a multi-agent Quantitative Structure-Activity Relationship (QSAR) classification system for tyrosinase inhibitor identification, in which the individual QSAR outputs are the inputs of a fusion approach based on the voting mechanism. The individual models are based on TOMOCOMD-CARDD (TOpological Molecular COMputational Design-Computer Aided Rational Drug Design) atom-based bilinear descriptors and Linear Discriminant Analysis (LDA) on a novel enlarged, balanced database of 1,429 compounds within 701 greatly dissimilar molecules presenting anti-tyrosinase activity. A total of 21 adequate models are obtained taking into account the requirements of the Organization for Economic Cooperation and Development (OECD) principles for QSAR validation and present global accuracies (Q) above 84.

Ligand-based computer-aided discovery of tyrosinase inhibitors. Applications of the TOMOCOMD-CARDD method to the elucidation of new compounds.

In this review an overview of the application of computational approaches is given. Specifically, the uses of Quantitative Structure-Activity Relationship (QSAR) methods for in silico identification of new families of compounds as novel tyrosinase inhibitors are revised. Assembling, validation of models through prediction series, and virtual screening of external data sets are also shown, to prove the accuracy of the QSAR models obtained with the TOMOCOMD-CARDD (TOpological MOlecular COMputational Design-Computer-Aided Rational Drug Design) software and Linear Discriminant Analysis (LDA) as statistical technique.

TOMOCOMD-CAMPS and protein bilinear indices--novel bio-macromolecular descriptors for protein research: I. Predicting protein stability effects of a complete set of alanine substitutions in the Arc repressor.

Descriptors calculated from a specific representation scheme encode only one part of the chemical information. For this reason, there is a need to construct novel graphical representations of proteins and novel protein descriptors that can provide new information about the structure of proteins. Here, a new set of protein descriptors based on computation of bilinear maps is presented.

Quantitative structure-activity relationship modelling of the carcinogenic risk of nitroso compounds using regression analysis and the TOPS-MODE approach.

Worldwide, legislative and governmental efforts are focusing on establishing simple screening tools for identifying those chemicals most likely to cause adverse effects without experimentally testing all chemicals of regulatory concern. This is because even the most basic biological testing of compounds of concern, apart from requiring a huge number of test animals, would be neither resource nor time effective. Thus, alternative approaches such as the one proposed here, quantitative structure-activity relationship (QSAR) modelling, are increasingly being used for identifying the potential health hazards and subsequent regulation of new industrial chemicals.

Prioritizing Hits with Appropriate Trade-Offs Between HIV-1 Reverse Transcriptase Inhibitory Efficacy and MT4 Blood Cells Toxicity Through Desirability-Based Multiobjective Optimization and Ranking.

Nonnucleoside reverse transcriptase (RT) inhibitors (NNRTIs) constitute a promising therapeutic option for AIDS. However, the emergence of virus-NNRTIs resistance was found to be a major problem in the field. Toward that goal, a "knock-out" strategy stands out between the several options to circumvent the problem.

Design, Synthesis, and Evaluation of Antineoplastic Activity of Novel Carbocyclic Nucleosides.

Cancer is the leading cause of death among men and women under age 85. Every year, millions of individuals are diagnosed with cancer. But finding new drugs is a complex, expensive, and very time-consuming task.